急性缺血性脑卒中的重组组织型纤溶酶原激活剂静脉溶栓治疗与护理

目的 探讨急性缺血性脑卒中的静脉溶栓治疗及护理措施。方法 对39例发病在6h以内的急性缺血性脑卒中患者（A组），男27例，女12例，年龄50～75岁，静脉注射重组组织型纤溶酶原激活N（rt-PA）8mg，随后60rain内持续静脉泵入rt-PA42mg。溶栓后12h开始皮下注射依诺肝素，连续应用7d。溶栓前中后给予相应的护理监测和措施。非溶栓组（B组）39例，不用溶栓剂及依诺肝素（使用川芎嗪160mg静脉滴注，连续应用7d，其余治疗同溶栓组）。结果 rt-PA溶栓治疗后39例溶栓患者的神经功能缺损和患肢肌力均获得不同程度的改善，总显效率达79．4％，无护理并发症发生。结论 对发病6h以内的急性缺血性脑卒中患者应用rt-PA溶栓治疗，可降低患者神经功能缺损，最大限度地恢复脑的正常功能，效果满意安全。     

Cytokine and protease levels in healing and non-healing chronic venous leg ulcers

Abstract Leg ulcers present a common and recurring problem in older people creating discomfort and distress for the patient and a great cost to the health care services. Cultured keratinocyte grafts have been used by many investigators to stimulate healing of chronic venous ulcers. It has been proposed that they may do this by producing cytokines which modulate the healing process. However, the types and levels of cytokines in the leg ulcer fluid before and during healing arc not known. Wound fluid was collected from venous leg ulcers in 18 patients beneath occlusive Tega-derm? dressing for 4 to 6 h. The leg ulcers were divided on clinical criteria into ‘healing’ and ‘non-healing’. PDGF-AB, GM-CSE IL-1α, IL-1β. IL-6 and bFGF were measured by ELISA and the levels of IL-1α, IL-1β. and IL-6 were also measured using biological assays. The effect of leg ulcer wound fluid on fibroblast and keratinocyte proliferation was measured indirectly by ³H-thymidine incorporation and MTT assay. Total protein, albumin levels, fibronectin degrading activity and collagenase activity, both active and latent were measured. No statistically significant differences in the levels of cytokines or collagenase were identified between healing and non-healing leg ulcers in the sample of leg ulcers studied. However, this study does give valuable information concerning the levels of cytokines and collagenase in chronic leg ulcer wound fluid.     

Changes in quality of life for patients with chronic venous insufficiency,present or healed leg ulcers

Background: Patients with chronic leg ulcers are handicapped in daily life, both by physical complaints and social problems. The aim of our study was not only to assess a possible impairment of quality of life (QOL) of leg ulcer patients but also to evaluate if there is a real improvement of QOL after healing of the ulcer. Patients with chronic venous insufficiency served as the control group. We further analyzed if there were significant differences in the response between patients who were and were not performing compression therapy. Patients and method: We interviewed three groups of patients (active venous leg ulcer, healed venous leg ulcer and patients with chronic venous insufficiency using the ?Freiburger Life Quality Assessment für Venenerkrankungen“ (FLQAv). Results: Physical problems, daily handicaps and social problems all increased with age. Contrary to our expectations, healing of a leg ulcer did not lead to a significant increase in QOL. Instead, patients with active ulcers did not regard their QOL as lower than those in the other groups. Compression therapy also did not impair QOL in the three groups. Conclusion: Even though ulcer healing is an admirable goal, it does not necessarily lead to an improved QOL, probably because of the numerous comorbidi‐ties in this patient group. Nonetheless, it is important to control problems associated directly with the wound to allow ulcer patients to participate actively in everyday life and minimize social problems.     

Is there an easier way to autograft skin in chronic leg ulcers? ‘Minced micrografts’, a new technique

Background Chronic venous leg ulcers represent an urgent and increasing problem for public health. The use of skin autografts results in a greater therapeutic success in healing chronic ulcers. Objective A simple method of skin autografting that could permit a wider use of skin grafts in outpatients is needed. A new technique allowing skin autografting in a simple one‐step process, without complex surgical procedures or expensive technical supplies, is presented. Methods A small, full‐thickness skin specimen taken from the patient is finely minced and spread on his leg ulcer bed allowing to cover a surface many times wider than the sample itself. Results This method induces faster re‐epithelization of chronic leg ulcers that failed to heal despite good conservative local therapy and give the possibility to repair very large ulcers with small fragments of skin. A clinical case is shown as an example out of 20 ulcers we recently treated. Conclusion Our preliminary report shows that this technique results in a greater therapeutic success (18 of 20 cases) in healing chronic leg ulcers, a common pathology that often affects outpatients treated for very long periods at home or in the Dermatologist's office. In our experience, this new and successful reparative possibility makes ‘mince grafting’ a recommendable procedure.     

Monitoring wound healing of venous stasis leg ulcers by in vivo 31P magnetic resonance spectroscopy

Background/aims: Venous stasis ulcers is a frequent clinical problem. Objective techniques for characterization and monitoring of wound healing are needed including noninvasive study of biochemical changes associated with the healing process. ³¹P magnetic resonance spectroscopy was not used in the past to study human wound healing in vivo.
Methods: ³¹P magnetic resonance spectroscopy with study of intracellular pH, phosphocreatine, and the phosphocreatine/inor-ganic phosphate ratio was used. Six patients with venous leg ulcer and three controls were studied.
Results: Both intracellular pH, phosphocreatine and the phos-phocreatine/inorganic phosphate ratio were found sensitive indicators of wound healing. Surprisingly the intracellular pH in healing ulcers was in the alkali range.
Conclusion: ³¹P magnetic resonance spectroscopy was found useful for the study of biochemical changes associated with wound healing. pH in the alkali range was an unexpected observation.     

失血性休克血清对内皮细胞t-PA和PAI-1mRNA表达的影响

目的探讨失血性休克大鼠血清对大鼠主动脉内皮细胞（SVAREC）表达组织型纤溶酶原激活剂（t—PA）和纤溶酶原激活剂抑制物-1（PAI-1）的影响。方法建立失血性休克大鼠模型,取假休克组、休克组血清,并将胎牛血清作为正常对照组,无菌处理后加入到培养基,分别与内皮细胞分别培养6h、12h和18h,用逆转录-聚合酶链反应（RT—PCR）检测t—PA和PAI—1mRNA的表达。结果与正常对照组相比,休克组血清刺激SVAREC6h、18h后t—PAmRNA均升高。与正常对照组及假休克组相比,休克组血清刺激SVAREC12h后,PAI-1mRNA升高-P〈0．05）;培养18h后,与正常对照组比,PAI-1mRNA升高（P〈0．01）。结论失血性休克血清上调内皮细胞t—PA和PAI-1mRNA表达,提示休克血清对内皮细胞有损伤作用,休克中应注意保护内皮细胞。     

Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer

BACKGROUND: The pathology of chronic wounds is often characterized by elevated levels of proinflammatory cytokines [e.g. tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta], proteases [e.g. matrix metalloproteinases (MMPs)] and neutrophil elastase. MMPs specifically have been implicated by a number of studies as the major protease family responsible for the degradation of key factors critical to the ulcer's ability to heal. OBJECTIVES: To assess individual MMPs in chronic wound fluid (CWF) in order to develop improved treatments for chronic ulcers. METHODS: Collagen type I and IV zymography, immunoprecipitation followed by a substrate activity assay, and an indirect enzyme-linked immunosorbent assay were all used to analyse MMP levels in CWF. RESULTS: Our studies demonstrate that there is excessive protease activity in CWF compared with both human serum and acute wound fluid (AWF), which can be specifically attributed to MMPs as determined through a MMP-inhibitor study. Multiple MMPs were immunoprecipitated from the CWF samples and MMP-9 was identified as the predominant protease in CWF, with significantly elevated activity levels in CWF compared with AWF. In addition, the clinical status of the ulcer is directly associated with the amounts of MMP-9 present in the wound fluid. Therefore, this study suggests that higher levels of MMP-9 in chronic wound fluid correlate with a clinically worse wound. CONCLUSIONS: In view of these results, it is hypothesized that a specific inhibitor of MMP-9 could potentially be more therapeutically effective than general MMP inhibitors in modulating chronic ulcers towards a healing state.     

Tolerability and efficacy of N-chlorotaurine in comparison with chloramine T for the treatment of chronic leg ulcers with a purulent coating: a randomized phase II study

BACKGROUND: The well-known active chlorine compound chloramine T (CAT) with broad-spectrum antimicrobial activity is in common therapeutic use for leg ulcers with purulent coatings; however, this treatment is painful. The tolerability of the less aggressive N-chlorotaurine (NCT), an endogenous compound also produced in vivo by stimulated human granulocytes, could be superior. OBJECTIVES: To assess the tolerability and efficacy of NCT in the cleaning of purulent coatings in chronic leg ulcers in comparison with CAT. METHODS: In a double-blind, randomized phase IIb clinical study 40 patients were treated for a median of 7 days (range 3-14) with a 1% aqueous solution of either NCT (20 subjects) or CAT (20 subjects) by twice-daily application of dressings soaked in the test solutions. Criteria for evaluation of tolerability were intensity and duration of pain caused by the ulcer therapy and scores of tissue toxicity (necrosis, granulation tissue and re-epithelialization). Therapeutic efficacy was graded as scores of intensity of purulent coating of the ulcers. RESULTS: The concentration tolerated in vitro by human epidermoid carcinoma cells was at least 10-fold higher for NCT (0.01%) compared with CAT (0.0001-0.001%). There was significantly less pain caused by NCT compared with CAT (P < 0.05) on days 1 and 4 and a trend for a shorter duration of pain (P = 0.093). The scores of intensity of coating improved without difference in both treatment groups, whereas granulation and re-epithelialization appeared earlier in the NCT group (P < 0.05). Non-quantitative microbiological cultures from ulcer smears revealed persistence of colonization by bacterial species in approximately half of both treatment groups. CONCLUSIONS: Both active chlorine compounds were helpful in reducing purulent coatings. Because of its lower toxicity and better tolerability, NCT is of advantage in the treatment of leg ulcers.     

Synthesis and degradation of connective tissue macromolecules in pachydermoperiostosis (PDF): evidence for altered processing of plasminogen activator inhibitor-1 (PAI-1)

Abstract Pachydermoperiostosis (POP) is a hereditary disease with hy-perostosis, clubbing of fingers, coarse skin and thickening of bones. Previous studies have disclosed some abnormality in the connective tissue in these patients. The purpose of the present study was to investigate connective tissue pathology in one family with PDP using libroblasl cultures. Fibroblastic cells were established from both the affected and healthy looking skin of 2 patients with PDP, and the expression of types I and III collagen, 92 kDa and 72 kDa gelatinases, metalloproteinase inhibitor (TIMP-1), human retinoic acid receptor and transforming growth factor β (TGFβ) was analyzed. The modulation of glycoprolein synthesis, and of plasminogen activators and their inhibitors by TGFβin vitro were also studied. The results indicated that collagen genes and gelatinases were similarly expressed in PDP and control cells, as well as the human retinoic acid receptor. TGF-β stimulated, both in PDP cells and normal cells, the synthesis of fibroneclin, procollagen and plasminogen activator inhibitor-1 (PAI-1), but qualitative differences could not be found. Proteolytically processed forms of PAI-1 were detected in PDP cell lines.     

Beneficial effect of resin salve in treatment of severe pressure ulcers: a prospective, randomized and controlled multicentre trial

BACKGROUND: Resin salve of the Norway spruce (Picea abies) has been used in folk medicine to heal wounds and infections. OBJECTIVES: To study its clinical effectiveness in the treatment of pressure ulcers of the skin. METHODS: A prospective, randomized, controlled multicentre trial involving 37 patients with grade II-IV pressure ulcers in 11 primary care hospitals was carried out between 2005 and 2007. The ulcers were randomly allocated to receive either resin salve or sodium carboxymethylcellulose hydrocolloid polymer treatment. The inclusion criterion was grade II-IV pressure ulcer. Exclusion criteria were a life expectancy of less than 6 months or a malignant disease. The primary outcome measure was complete healing of the ulcer within 6 months. Secondary outcome measures were partial healing of the ulcer, and successful eradication of bacterial strains cultured from the ulcers at study entry. RESULTS: Thirteen patients of the resin group and nine patients of the control group completed the 6-month trial. All ulcers healed in 12 of the 13 patients (92%) in the resin group and in four of the nine patients (44%) in the control group (P=0.003; power 73%). Complete healing of the ulcers over time was significantly more common in the resin group than in the control group (P=0.013). Bacterial cultures from the ulcer area more often became negative within 1 month in the resin group. CONCLUSIONS: Traditional resin salve is significantly more effective in the treatment of infected and noninfected severe pressure ulcers than cellulose polymer gauzes.     

Angiopoietin‐1, angiopoietin‐2 and Tie‐2 receptor expression in human dermal wound repair and scarring

Background The angiopoietin (Ang)/Tie‐2 ligand/receptor system is known to interact with the vascular endothelial growth factor (VEGF) pathway to determine the fate of blood vessels during angiogenesis. However, the precise contribution of this system to angiogenesis and the mechanisms of vascular maturation and remodelling in human tissue repair have yet to be elucidated. Objectives To examine the spatial and temporal expression of Ang‐1, Ang‐2, Tie‐2 and VEGF in relation to angiogenesis in human surgical wounds. Methods Punch biopsies were taken either from normal unwounded skin (controls) during surgery or from mastectomy scars between 3 days and 2 years postsurgery. Ang‐1, Ang‐2, Tie‐2 and VEGF fibroblast/myofibroblast and endothelial expression were characterized by immunohistochemistry, analysed semiquantitatively and correlated with microvessel density (MVD) and scar age. Results The expression of VEGF, Ang‐1, Ang‐2 and Tie‐2 in fibroblasts/myofibroblasts was increased significantly in early scars, decreased in older scars and was related to scar age (P < 0·001) and MVD (P < 0·0004), with strong correlations between all factors. In contrast, vascular expression of Ang‐1 was decreased slightly in early scars, vascular Ang‐2 remained constant and Tie‐2 vascular expression increased, although there were no correlations with scar age or MVD. Conclusions These data demonstrate that angiopoietins and their receptor, Tie‐2, are expressed in both fibroblasts/myofibroblasts and endothelial cells in healing human wounds. Fibroblast/myofibroblast expression correlates with angiogenesis and VEGF expression, suggesting a role for the angiopoietin/Tie‐2 system in normal wound repair and scarring.     

Squamous cell carcinoma complicating chronic venous leg ulceration: a study of the histopathology, course and survival in 25 patients

We have studied 25 cases of squamous cell carcinoma in chronic venous leg ulcers. Twenty-three of the patients were dead and two were alive. The mean age at cancer diagnosis was 78.5 years. The median survival was 1 year. Eleven tumours were well-differentiated, 10 moderately and four poorly. All patients with a poorly differentiated tumour died within a year. Metastases were certain in eight cases. The disease was lethal in 10 cases which included all poorly differentiated tumours. The survival of the study group was significantly shortened compared with a control group of patients with lower limb non-melanoma skin cancer (n = 433) from the Swedish Cancer Registry (P = 0.0084). When diagnosed, squamous cell carcinoma in chronic leg ulcers merits a thorough investigation of the degree of differentiation and spread. Assertive treatment is indicated as poorly differentiated tumours and some moderately differentiated tumours may be fatal.     

Increased expression of platelet-derived growth factor receptor alpha and beta and vascular endothelial growth factor in the skin of patients with chronic venous insufficiency

Abstract Growth factors produced by a variety of cells act as signalling peptides through specific cell surface receptor pathways. Functions such as cell proliferation, migration and differentiation have been assigned to each of them. Here, we report alterations of platelet-derived growth factor receptor alpha (PDGFR-α) and beta (PDGFR-β) and vascular endothelial growth factor (VEGF) expression patterns in the progressive clinical stages of chronic venous insufficiency (CVI). A total of 30 punch biopsies were taken from patients with CVI, and VEGF and PDGFR were detected by indirect immunofluorescence and immunoperoxidase techniques. PDGFR-α and PDGFR-β expression was strongly increased in endothelial cells of capillaries, pericapillary cells and connective tissue cells in the stroma of the skin of venous eczema and venous leg ulcer patients, and to a smaller extend in the dermis of those with lipodermatosclerosis. VEGF staining showed a similar expression pattern in the progressive CVI stages. However, staining of vessels in particular might simply reflect binding of VEGF, secreted by keratinocytes or fibroblasts, to its receptors. Growth factor and receptor expression in specimens from telangiectases and reticular veins, and from pigmented areas, resembled that of normal skin. We conclude that PDGFR-α, PDGFR-β and VEGF play an important role in mediating inflammation and epithelial hyperproliferation in venous eczema, inducing connective tissue sclerosis in lipodermatosclerosis, and causing the reduced reepithelialization tendency in venous ulcers. We speculate that endothelial proliferation with chronic venous hypertension might be mediated by these growth factors. Received: 1 April 1997     

Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line

We showed previously that pemphigus IgG enhanced both the activity of urokinase plasminogen activator (uPA) in cultured cells and the expression of its receptor (uPAR) on uPA-binding keratinocytes. In the present study, to clarify whether uPAR and uPA-activated plasmin are actually involved in the blistering process after pemphigus IgG binding to the cell surface, we examined the effects of the following on uPAR expression and on cell-cell detachment in DJM-1 cells, a squamous cell carcinoma line: (i) phosphatidylinositol-specific phospholipase C (PI-PLC) - which releases uPAR from the membrane surface into the culture medium by cleaving the glycosylphosphatidylinositol anchor thus inhibiting uPAR activity, and (ii) uPA inhibitors (tranexamic acid, aprotinin, p-aminobenzonic acid and dexamethasone). Preincubation with PI-PLC decreased dramatically the pemphigus IgG-induced uPAR expression in a dose-dependent manner, and inhibited pemphigus IgG-induced cell-cell detachment at 10 microg/mL. On the other hand, tranexamic acid (15 mM) inhibited pemphigus IgG-induced cell-cell detachment without reduction of uPAR expression, although aprotinin, p-aminobenzonic acid and dexamethasone failed to alter either of these parameters. Although uPAR expression on the pemphigus IgG-bound cell surface and uPA activation may contribute significantly to the pathogenesis of acantholysis in pemphigus, the mechanisms are complicated and should be defined further.     

The expression of cytokines, growth factors and ICAM-1 in the healing of human cutaneous xenografts on nude mice

Abstract We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of human skin grafted onto athymic nude mice. Signs of healing of grafts were visible clinically around 3–5 days post-graft and were completed by 4 weeks post-graft. During the Ist 2 weeks, we observed the following, (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers, (ii) Langerhans cells were not detectable wilh anti-human CDIa antibodies during the first week of healing but were clearly detectable 2 weeks post-graft, (iii) DOPA (dihydroxy phenyl-alanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-l (IL-I) was clearly detected in some basal cells of the epidermis, especially in melanoeytes and some keratinocytes during the early stage of healing. Transforming growth factor-α: (TGF-(α) was detected in epidermis first in melanocytes and some kera-tinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided wilh kera-tinocyte proliferation and melanocyte migration. TGF-β was strongly ex-pressed in the epidermis and dermis after the first week post graft, (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are ex-pressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.     

止痛生肌散联合生肌象皮膏对下肢静脉痛性溃疡治疗前后MMP-1、MMP-2及相关TIMPs的影响

目的评价止痛生肌散联合生肌象皮膏对下肢静脉痛性溃疡治疗前后伤口渗出液和组织中MMP-1、MMP-2及相关TIMPs的影响。方法应用DESIGN工具筛选出符合条件的小腿静脉痛性溃疡患者32例,收集止痛生肌散联合生肌象皮膏治疗前、后渗出液和组织,同时收集32例乳腺癌术后伤口渗出液作为急性疮面参照对象,分别采用酶联免疫吸附试验和Western blot检测渗出液和组织中MMP-1、MMP-2及相关TIMPs浓度。结果渗出液和组织中MMP-1、MMP-2、TIMP-1、TIMP-2、MMP-2/TIMP-2水平经"去腐止痛"治疗后均呈明显下降趋势,各检测指标0 d与6 d相比差异存在统计学意义(P<0.001)。治疗前后0 d、6 d渗出液与组织中MMP-1、MMP-2、TIMP-1、TIMP-2、MMP-2/TIMP-2水平均存在正相关(P<0.001)。结论止痛生肌散联合生肌象皮膏治疗下肢痛性溃疡的机制为实现慢性疮面急性化,通过降低MMP-1、MMP-2及相关TIMPs含量实现疮面愈合。     

慢性荨麻疹患者红细胞补体受体1分子表达及外周血IgE和补体C3、 C4水平的相关性研究

目的 探讨红细胞补体受体1(CR1)在慢性荨麻疹发病机制中的作用及意义.方法 慢性荨麻疹患者59例,其中含人工划痕症14例,慢性特发性荨麻疹45例,采用流式细胞仪检测外周血红细胞CR1的表达,并采用双抗体夹心酶联免疫吸附法(ELISA)检测外周血补体C3、C4、CH50及IgE水平.29例健康人作为对照组.利用ONE-WAY ANOVA进行三组样本间均数比较,两组均数的比较采用独立样本t检验,相关分析采用Pearson相关分析法.结果 外周血红细胞CR1的表达水平人工划痕症组为35.06±2.06(10 000个红细胞表面的荧光强度)、慢性特发性荨麻疹组为29.17±1.53,均高于健康对照组(20.46±2.57),t值分别为4.20、3.33,P值均＜0.05,人工划痕症组与慢性特发性荨麻疹组间差异无统计学意义(P＞0.05).外周血IgE水平人工划痕症组为(769.89±123.06) μg/L,慢性特发性荨麻疹组为(340.09±29.74) μg/L,均高于健康对照组(107.63±88.79μg/L),t值分别为5.58、5.85,P值均＜0.05,人工划痕症组高于慢性特发性荨麻疹组(t=3.49,P＜ 0.05).慢性荨麻疹患者中IgE为0～240 μg/L的22例患者CR1水平(24.45±10.83)与IgE为500 μg/L以上的17例患者CR1水平(33.09±11.86)差异有统计学意义(t=3.33,P＜0.05).血清总IgE与CR1水平呈显著正相关(r=0.27,P＜ 0.05),与C3(r=0.16,P＞ 0.05)、C4(r=-0.08,P＞ 0.05)均无相关性.C3与C4具有正相关(r=0.54,P＜ 0.01).3组C3、C4和CH50水平经ONE-WAY ANOVA检验,差异均无统计学意义(P＞0.05).结论 红细胞CR1在慢性荨麻疹患者中的表达存在异常.